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Potentially increased sensitivity of pregnant and lactating female rats to immunotoxic agents

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Author: Menke, A. · Wolterbeek, A. · Snel, C. · Bruijntjes, J. · Groot, D.D. · Oostrum, L.V. · Waalkens, I. · Kuper, C.F.
Source:Toxicologic Pathology, 2, 40, 255-260
Identifier: 447346
doi: doi:10.1177/0192623311428476
Keywords: Biology · DOTC · immunotoxicity · lactation · pregnancy · sensitive periods · thymus · Healthy for Life · Healthy Living · Life Triskelion · QS - Quality & Safety · EELS - Earth, Environmental and Life Sciences TNO Bedrijven


Characteristic susceptibility to environmental and pharmaceutical exposure may occur during periods in life of marked histophysiological changes of the immune system. Perinatal development is such a period; pregnancy followed by lactation is potentially another one. Here, we explored the influence of pregnancy and lactation on the model immunotoxic compound di-n-octyltin dichloride (DOTC) in rats using clinical and histopathological parameters. Female rats were exposed to 0, 3, 10, or 30 mg DOTC/kg feed during pregnancy and up to 20 (at weaning) or 56 days after delivery. Age-matched nonmated females were exposed during the same time periods. DOTC at the level of 10 and 30 mg/kg decreased thymus weight and affected thymus morphology in the lactating rats. In addition, DOTC decreased the numbers of neutrophils in the lactating rats. These effects were no longer apparent at day 56 despite continuous exposure to DOTC. This explorative study indicates that the innate and adaptive immune system may be especially sensitive to immunotoxicants during pregnancy and lactation. © 2012 Society of Toxicologic Pathology.